NDLI: Assessment of Resistance Mechanisms and Clinical Implications in Patients with KRAS Mutated-Metastatic Breast Cancer and Resistance to CDK4/6 Inhibitors

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Assessment of Resistance Mechanisms and Clinical Implications in Patients with KRAS Mutated-Metastatic Breast Cancer and Resistance to CDK4/6 Inhibitors

Content Provider	MDPI
Author	Raimondi, Lucrezia Raimondi, Filippo Pietranera, Marta Rocco, Arianna Di Benedetto, Laura Di Miele, Evelina Lazzeroni, Rachele Cimino, Giuseppe Spinelli, Gian
Copyright Year	2021
Description	Despite therapeutic improvements, resistance to palbociclib is a growing clinical challenge which is poorly understood. This study was conducted in order to understand the molecular mechanisms of resistance to palbociclib, and to identify biomarkers to predict who will take advantage from cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). A total of about a thousand blood samples were collected from 106 patients with hormone receptor positive (HR+) human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer who received palbociclib in combination with fulvestrant as the first-line metastatic therapy enrolled in this study. The genotyping of their plasma cell-free DNA was studied, including serial plasma samples. Collectively, our findings identify the appearance of KRAS mutations leading to palbociclib resistance acquisition within 6 months, and provide critical information for the prediction of therapeutic responses in metastatic breast cancer. By monitoring KRAS status through liquid biopsy, we could predict who will take advantage from the combination of palbociclib and fulvestrant, offering highly-individualized treatment plans, thus ensuring the best patient quality of life.
Starting Page	1928
e-ISSN	20726694
DOI	10.3390/cancers13081928
Journal	Cancers
Issue Number	8
Volume Number	13
Language	English
Publisher	MDPI
Publisher Date	2021-04-16
Access Restriction	Open
Subject Keyword	Cancers Oncology Metastatic Breast Cancer Targeted Therapy Kras Cdk4/6 Inhibitors Liquid Biopsy Ddpcr Resistance Mechanisms
Content Type	Text
Resource Type	Article

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